Fri Jul 01 2022

80 articles - From Friday Jun 24 2022 to Friday Jul 01 2022

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Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…

Blood

International Consensus Classification of Myeloid Neoplasms and Acute Leukemia: Integrating Morphological, Clinical, and Genomic Data.

Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.

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Blood Adv

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients

This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related critical illness.

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Blood Cancer J

Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee.

Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.

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Meta-analysis

meta-analyses and systematic reviews


Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

Chronic Myeloid Leukemia: 2022 Update on Diagnosis, Therapy and Monitoring.

Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least 2 TKIs, and for al patients in advanced phase disease. Older patients who have a cytogenetic relapse post failure on al TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non-TKI anti-CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, busulfan, others).

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Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease.

These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with chronic kidney disease: increased endogenous erythropoietin production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.

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HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy.

We also provide in vitro data supporting the functionality of HERV-specific CD8 + T-cells against AML cells. These results show that HERVs represent an important source of genetic information that can help enhancing disease stratification or biomarker identification and an important reservoir of alternative tumor-specific T cell epitopes relevant for cancer immunotherapy.

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Ann Oncol

Nivolumab + low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142.

The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.

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Blood

Aberrant expansion of spontaneous splenic germinal centers induced by hallmark genetic lesions of aggressive lymphoma.

Mice carrying al four genetic lesions showed a greater than 50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCB as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.

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GGCX mutants that impair hemostasis reveal the importance of processivity and full carboxylation to VKD protein function.

g. warfarin therapy or vitamin K deficiency.

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Liver to lung microembolic NETs promote Gasdermin-D-dependent inflammatory lung injury in Sickle Cell Disease.

Remarkably, these NETs travel intravascularly from liver to lung, where they promote neutrophil-platelet aggregation and the development of acute lung injury. This study introduces a novel paradigm that liver to lung embolic translocation of NETs promotes pulmonary vascular vaso-occlusion, and identifies a new GSDMD-mediated, P-selectin-independent mechanism of lung injury in SCD.

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Protein tyrosine phosphatase PTPN22 negatively modulates platelet function and thrombus formation.

Furthermore, inhibition of PTPN22 enhanced human platelet aggregation, spreading, clot retraction and increased PDE5A phosphorylation (Ser92). In conclusion, our study demonstrates a novel role of PTPN22 in platelet function and arterial thrombosis, identifying new potential targets for future prevention of thrombotic or cardiovascular diseases.

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Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase III trial in mantle cell lymphoma.

Study can be found in EudraCT N. 2009-012807-25

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Specification of hematopoietic stem cells in mammalian embryos: A rare or frequent event?

Here, we explore recent advances in understanding the numbers and kinetics of cells that emerge during development to support lifelong hematopoiesis-advances that are made possible by new technologies allowing interrogation of lifelong blood potential without embryo perturbation or transplantation. Illuminating the dynamics of these cells during normal development informs efforts to better understand the origins of hematologic disease and engineer HSCs from differentiating pluripotent stem cells.

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STAT1 is essential for HSC function and maintains MHCIIhi stem cells that resists myeloablation and neoplastic expansion.

Similar to mice, high MHCII expression is a feature of human HSCs residing in a deeper quiescent state. Our results therefore position STAT1 at the interface of stem cell heterogeneity and the interplay between stem cells and the adaptive immune system, areas of broad interest in the wider stem cell field.

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Targeted Radiotherapy for Early-Stage Low-Risk Pediatric Hodgkin Lymphoma Slow Early Responders: A COG AHOD0431 Analysis.

Radiotherapy remains an important component of treatment for patients who are SER. Trial Registration: Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients with Newly Diagnosed Hodgkin's' Lymphoma; NCT00302003.

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Whole-genome CRISPR screening identifies N-glycosylation as a genetic and therapeutic vulnerability in CALR-mutant MPN.

We found that N-glycosylation inhibition significantly reduced CFU-MK formation in patient-derived CALR-mutant bone marrow, as compared to bone marrow-derived from healthy donors. In aggregate, our findings advance the development of clonally selective treatments for CALR-mutant MPN.

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Blood Adv

Anchoring IgG-degrading enzymes to the surface of platelets selectively neutralizes antiplatelet antibodies.

Treatment of mice expressing human FcRIIA with scIV.3-IdeS reduced thrombocytopenia in a model of ITP and significantly improved the half-life of transfused platelets expressing human FcRIIA. Together, these data suggest that scIV.3-IdeS can selectively remove pathogenic antiplatelet IgG and may be a potential treatment for patients with ITP and severe bleeding.

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COVID-19 and Venous Thromboembolism Risk in Patients With Sickle Cell Disease.

After adjusting for differences in baseline characteristics, no significant differences in VTE rates within 6 months were found between the two groups (adjusted-RR=1.06 (95% Confidence Interval: 0.79-1.41)). These data suggest that hospitalization with COVID-19 does not further increase VTE risk in patients with SCD.

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Defective VWF secretion due to the expression of MYH9-RD E1841K mutant in endothelial cells disrupts hemostasis.

Finally, we present mechanistic findings that E1841K mutation not only interferes with S1943 phosphorylation and impairs the peripheral distribution of Rab27a positive WPBs in ECs under quiescent condition, but also interferes with S1916 phosphorylation by disrupting the interaction with zyxin and CKIIa, and reduces actin framework formation around WPBs and subsequent VWF secretion under the stimulation by a cAMP agonist. Altogether, our results suggest that impaired cAMP-induced endothelial VWF secretion by E1841K mutant expression may contribute to the MYH9-RD bleeding phenotype.

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Development of a Carotid Artery Thrombolysis (iCAT) Stroke Model in Mice.

These studies confirm the benefits of anticoagulants in enhancing thrombolysis and large artery recanalization, however at high levels of anticoagulation (~3-fold prolongation of APTT), this effect is offset by increased incidence of carotid artery embolization and distal middle cerebral artery occlusion. The iCAT stroke model should provide important new insight into the effects of adjunctive antithrombotic agents on real-time thrombus dynamics during thrombolysis, and their correlation with stroke outcomes.

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Improvement of Hemolytic Anemia with GBT1118 is Reno-protective in Transgenic Sickle Mice.

This study provides mechanistic insights into potential reno-protective effects of strategies which mitigate hemolysis in SCA. Studies in humans are needed to confirm our findings.

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Improvements in allogeneic hematopoietic cell transplantation outcomes for adults with ALL over the past 3 decades.

Allo-HCT outcomes for adults with ALL have improved over the past 30 years. Improved outcomes in the future will require more effective prevention of relapse in patients with ALL not in CR1 and in those with high-risk chromosomal abnormalities.

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Metabolic reprogramming under hypoxic storage preserves faster oxygen unloading from stored red blood cells.

Correlations between gas-handling and lipidomic changes were modest. Thus, hypoxic storage of RBCs preserves key metabolic pathways and O2 exchange properties, thereby improving the functional quality of blood products and potentially influencing transfusion outcomes.

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Outcomes of elderly diffuse large B-cell lymphoma patients treated with R-CHOP: 10-year follow-up of the LNH03-6B trial.

Progression/relapse led to poor prognosis after second-line chemotherapy in the pre-CAR-T era. Novel approaches in first-line and alternative treatments in second-line treatments are warranted in this population.

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Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis.

Given the favorable toxicity profile, an important advantage for the typically frail AL population, further evaluation of the ixazomib in other combinations in the upfront setting is warranted. This trial is registered at as NCT01864018.

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Refining the migration and engraftment of short-term and long-term HSCs by enhancing homing-specific adhesion mechanisms.

Remarkably, fucosylation of Flk2negCD34pos ST-HSCs consistently led to their ability to transplant secondary recipients, the gold standard for testing functionality of LT-HSCs. These data suggest that treatments to overcome the molecular disparity in adhesion mechanisms among ST-HSCs and LT-HSCs, differentially influences their abilities to migrate and engraft in vivo and boosts ST-HSCs engraftment in vivo.

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Romiplostim addition to conditioning prior to HSCT allows chemotherapy reduction while maintaining engraftment levels.

We thus tested if the addition of Romiplostim to the clinically applied conditioning chemotherapy regimen cyclophosphamide and busulfan leads to increased efficacy of the chemotherapeutic regimen. We found that Romiplostim not only sensitizes HSCs to chemotherapy but also enables a reduction of the main chemotherapeutic component Busulfan by half, while HSC engraftment levels are maintained in long-term, serial transplantation assays.

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The identification of TCF1+ progenitor exhausted T cells in THRLBCL may predict a better response to PD-1/PD-L1 blockade.

Of therapeutic relevance, we validated our results by immunohistochemistry, identifying a subset of TCF1+ progenitor exhausted T-cells enriched in THRLBCL patients. This subset of TCF1+ exhausted T-cells correlates with good clinical response to immune checkpoint therapy and may improve prediction of anti-PD-1 response in THRLBCL patients.

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Blood Cancer J

A multiparametric niche-like drug screening platform in acute myeloid leukemia.

In this cohort, a 23-drug screen nominated ruxolitinib as a sensitizer to anthracycline-cytarabine. This finding was validated in an NPM1c PDX model.

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Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia.

GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.

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CA Cancer J Clin

Cancer treatment and survivorship statistics, 2022.

CA Cancer J Clin. 2022; 72:000-000.

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Haematologica

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.

None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs 73%, p=0.003, and 42% vs 16%, p.

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Clinical features of hepatitis E infections in patients with hematological disorders.

Nevertheless, since mortality from the progression of hematological disease was higher than hepatitis E-related mortality, we suggest a careful case-by-case decision of cancer-treatment modification. Patients in post-treatment follow-up phase may also suffer from severe courses and hepatitis E chronification occurs as frequently as in patients undergoing active therapy.

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Combination elotuzumab and lenalidomide treatment efficacy is dependent on crosstalk between NK cells, monocytes and myeloma cells.

In conclusion, our findings suggest that MM patients require Elo and Len-mediated upregulation of CD54 on the autologous myeloma cells, in combination with NK cells and monocytes to mediate an effective anti-tumour response. Further, our data suggest that increased myeloma cell CD54 expression levels could be a powerful predictive biomarker for response to Elo and Len treatment.

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Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modelling.

We confirm significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome, this knowledge may help guide clinical decisions on transplant strategy.

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Double punch for plasma cell leukemia.

Not available.

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IgM monoclonal gammopathies of clinical significance: diagnosis and management.

A multidisciplinary approach is required particularly for IgM-related neuropathies and Schnitzler syndrome. Future work exploring novel clone directed agents and pathogenetic IgM-directed therapies is welcomed.

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Molecular predictors of response to venetoclax plus hypomethylating agent in treatment-naïve acute myeloid leukemia.

Not available.

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Myeloablative fractionated busulfan conditioning regimen with post-transplant cyclophosphamide in HLA matched and haploidentical transplantation: results of a phase II study.

Not available.

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Plasma cell leukemia: another piece of the puzzle.

Not available.

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Routine clinical parameters and laboratory testing predict therapy related myeloid neoplasms after treatment for breast cancer.

Of the 206 BC patients who underwent BMBx included in our study, 107 had t-MN. By multivariable analysis, white blood cell count 4-11 K/mcL, absolute neutrophil count (ANC) /1.5 K/mcL, hemoglobin h12.2 g/dL, red cell distribution width 11.5-14.5%, the presence of bone metastasis and a time from BC diagnosis to BMBx.

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Leukemia

Rare germline alterations of myeloperoxidase predispose to myeloid neoplasms.

This finding also correlated with increased clonogenic potential after serial replating in the setting of H -induced DNA damage and activation of error-prone DNA repair may result in secondary genetic damage potentially predisposing to leukemia leukemic evolution. In conclusion, our study for the first time demonstrates that germline MPO variants may constitute risk alleles for MN evolution.

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Thromb Haemost

Long-Read Sequencing Identifies the First Retrotransposon Insertion and Resolves Structural Variants Causing Antithrombin Deficiency.

The nucleotide-level resolution achieved for al SVs allowed breakpoint analysis, which revealed repetitive elements and microhomologies supporting a common replication-based mechanism for al the SVs. Our study underscores the utility of long-read sequencing technology as a complementary method to identify, characterize, and unveil the molecular mechanism of disease-causing SVs involved in ATD, and enlarges the catalogue of genetic disorders caused by retrotransposon insertions.

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Treatment and bleeding complications of cancer-associated venous thromboembolism: A Korean population-based study.

DOACs have become the most prescribed anticoagulant in CAT. Bleeding was more prevalent with DOAC than PAC. The bleeding complications should be carefully monitored to ensure optimal treatment, especially with DOAC.

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Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

The deleterious effect of acetaminophen in cancer immunotherapy.

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Blood

A tale of two alleles: TP53 and transformation in MPNs.

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CAR T-cell therapy: which product for which patient?

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Ceramide: improving Bcl-2 inhibitor therapy.

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Highjacking myeloma's niche with beefed-up CAR-Ts.

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Mechanisms of resistance to mogamulizumab.

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Pain without gain: steroids and sickle crisis.

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Phagocytosing with TP53 and extracellular vesicles.

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Smart salvage treatment for Hodgkin lymphoma.

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Zinc: a damage signal promoting thymic repair.

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J Hematol Oncol

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling.

Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment.

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Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

Clinical Features Associated with Thrombotic Events in Children with Myeloproliferative Neoplasms.

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Comprehensive assessment of cognitive function in adults with moderate and severe sickle cell disease.

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Real-life incidence of thrombotic events in leukemia patients treated with ponatinib.

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Ann Oncol

Mature tertiary lymphoid structure is a specific biomarker of cancer immunotherapy and does not predict outcome to chemotherapy in non-small cell lung cancer.

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Single cell heterogeneity and evolution of breast cancer bone metastasis and organoids reveals therapeutic targets for precision medicine.

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Blood Cancer J

Clinical and therapeutic implications of BRAF fusions in histiocytic disorders.

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Clinical outcome of myelodysplastic syndrome progressing on hypomethylating agents with evolving frontline therapies: continued challenges and unmet needs.

Pubmed   Journal   ReadQx   PMC

Haploidentical vs matched sibling donor transplant for paroxysmal nocturnal haemoglobinuria: A multicenter study.

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Others

all remaining publications eg case reports, images of the month, etc…

Blood

Al-Sawaf O, Lilienweiss E, Bahlo J, et al. High efficacy of venetoclax plus obinutuzumab in patients with complex karyotype and chronic lymphocytic leukemia. Blood. 2020;135(11):866-870.

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Dysplastic megakaryocytes in dyskeratosis congenita with variant in PARN.

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Farley A, Lloyd S, Dayton M, Biben C, Stonehouse O, Taoudi S. Severe thrombocytopenia is sufficient for fetal and neonatal intracerebral hemorrhage to occur. Blood. 2021;138(10):885-897.

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Introduction to a review series on pediatric hematology.

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Liu Y, Chen Q, Jeong H-W, et al. Dopamine signaling regulates hematopoietic stem and progenitor cell function. Blood. 2021;138(21):2051-2065.

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Plasma cell leukemia with small cell morphology.

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Thrombopoietin receptor agonists in adult Evans syndrome: an international multicenter experience.

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Unexpected presentation of cold agglutinin syndrome with B-acute lymphoblastic leukemia.

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Blood Adv

Differential regulation of CTLA4 expression through BTK-dependent and independent mechanisms in CLL.

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Emerging Clinical Trial Designs May Accelerate Translation in Hematology: Lessons from COVID-19.

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Revision of RUNX1 Variant Curation Rules.

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RR6 prognostic model provides information about survival in myelofibrosis treated with ruxolitinib: validation in a real-life cohort.

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Venetoclax retreatment of patients with chronic lymphocytic leukemia after a previous venetoclax-based regimen.

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Blood Cancer J

Outcomes and patterns of treatment in chronic myeloid leukemia, a global perspective based on a real-world data global network.

Pubmed   Journal   ReadQx   PMC

Lancet Haematol

European Hematology Association Hybrid Congress 2022.

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Leukemia

Changes in multiple myeloma treatment patterns during the early COVID-19 pandemic period.

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Sequential treatment with bendamustine, obinutuzumab (GA101) and Ibrutinib in chronic lymphocytic leukemia (CLL): final results of the CLL2-BIG trial.

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